Dr. Albert Badia is leading her own laboratory together with Dr. Albert Badia, focussing on Neuropharmacology:
The main goal of the Neuropharmacology Grup is to study the activity and fucntions of Acetilcolinesterase (AChE) and its inhibition by acetylcholinesterase inhibidors, currently, the most successful treatment for Alzheimer disease. Considering the mechanism of action for the acetylcholinesterase inhibitors (AChEI), they are expected only to temporarily mitigate some of the symptoms. However, some clinical studies have shown that AChEI not only are able to increase ACh viability in AD patients but also could act as modifying-disease drugs. On the other hand, AChE occurs in neuronal and non-neuronal tissue developing non-canonical functions as well. These not-catalytic functions are involved in morphogenesis, hematopoiesis, osteogenesis, apoptosis, and in neurogenesis. These functions have been ascribed to a two variant of AChE: 'Synaptic' AChE-S a membrane multimeric enzyme and the soluble monomeric 'readthrough' AChE-R. In general, both AChE isoforms are inducible by neural injury or by cholinesterase inhibitors, however, the expression of AChE-R appears to be related to neuroprotection and repair, whereas AChE-S is more highly associated with injury and increasing neurotoxicity. Accordingly, the main aim of the present project is to analyze the effect of AChE inhibitors (huprines and heterodimers) on the two variants of AChE (-S and –R) expression under different experimental conditions and approaches, in vivo and in vitro, taking into account both neurotoxic and neurogenesis process. This objective will allow us to go more deeply into the mechanism of action of AChEIs and also to get additional information about role and functions of AChE isoforms.
On the other had, and in colaboration with the Chemical Pharmaceutic group of Faculty of Pharmacy at Barcelona University, we characterize the pharmacological profile of new heterodimers compound with multitarged functions, related all of them to the neuropathological factors involved in the Alzheimer disease.
MAIN RESEARCH LINES
1) Cholinergic system in the development of Alzheimer’s disease: Role of different AChE variants and anticholinesterasic drugs in neurogenesis and neurodegeneration processes.
2) Pharmacological evaluation of new multifunctional drugs
• Pera M., Camps P., Munoz-Torrero D., Perez B., Badia A.,Clos MV. Undifferentiated and Differentiated PC12 Cells Protected by Huprines Against Injury Induced by Hydrogen Peroxide. PloS ONE 8(9): e74344.2013
• Ratia M, Giménez-Llort L, Camps P, Muñoz-Torrero D, Pérez B, Clos MV, Badia A. Huprine X and Huperzine A Improve Cognition and Regulate Some Neurochemical Processes Related with Alzheimer's Disease in Triple Transgenic Mice (3xTg-AD). Neurodegener Dis. 2013;11(3):129-40.
• Galdeano C, Viayna E, Sola I, Formosa X, Camps P, Badia A, Clos MV, Relat J, Ratia M, Bartolini M, Mancini F, Andrisano V, Salmona M, Minguillón C, González-Muñoz GC, Rodríguez-Franco MI, Bidon-Chanal A, Luque FJ, Muñoz-Torrero D. Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases. J Med Chem. 2012 26;55(2):661-9.